Perspectives on where our world is heading from a vantage point in Denver, Colorado.

10 June 2010

More Progress On A Genetic Model For Autism

New studies that link specific locations in the genome with autism largely confirm previous studies (see also here regarding the heritability of Asperger's Syndrome).

Studies of identical twins show that when one twin has autism, about 90 percent of the time the other twin will too. Autism affects about one in every 100 children in the United States and is more common in boys. . . the new study shows that people with autism had the same number of deletions [ed. i.e. places where DNA is usually present] as people in a healthy control group did. However, people with autism tend to have deletions that remove parts or all of genes, while healthy people carry deletions on stretches of DNA that don’t contain genes.

“You and I may have just as many deletions in our genomes, but since they don’t hit genes, we don’t have autism. . . . This is a natural part of being a human being. We get mutations. Most of the time it’s not a problem, but sometimes it hits a gene involved in autism.” . . .

Many of the people with autism had more than one spot in the genome where they were missing large chunks of DNA, each about 30,000 base pairs long.

Each of the specific variants was rare on its own, with even the most common found in less than 1 percent of people in the study. Often, people with autism inherited the rare variants from their parents, but just under 6 percent of them had new deletions not found in their parents. Such new mutations may account for some sporadic cases of autism. . . . “Most individuals with autism are genetically unique," . . . Although each person with autism appears to have a distinct set of genetic variations, the genes affected by the variants tend to affect similar biological processes. . . .

Some of the deleted genes had a strong link to autism, meaning that missing just a single copy is enough to push a person across the autism threshold. . . . Other genes had to be inherited along with more deletions or other genetic factors for autism to develop.

One gene strongly linked to autism in the new study is called DDX53-PTCHD1, and is located on the X chromosome. Women — who have two X chromosomes — may carry a deletion of the gene on one of their X chromosomes, but a healthy copy of the gene on the other X chromosome is enough to cover for the missing copy. Problems may arise if a woman passes the X chromosome with the deleted gene on to a son. With no healthy copy of the gene (the Y chromosome doesn’t carry the gene) to compensate, he will get autism.

All together, the new study identified 25 places in the genome that may help in diagnosing autism. . . . Even with the new findings, scientists are able to explain genetic causes for only about 10 percent of autism cases. . . . “What causes autism in the other 90 percent of cases is still on the table[.]”

1. Autism has a strong genetic component.

2. Autism involves a variety of genetic causes, a significant number of which are either new mutations in the child's generation, or are asymptomatic until combined in rare ways with other genes. The present as a single syndrome only because they all impact genes related to brain function.

3. Some important element of autism genetics is linked to an X chromosome genetic factor.

The genetic model of autism shows some similarity with schitzophrenia and bipolar disorder, which seems to be the cumulative result of large numbers of more or less random variations in the genome, rather than having a single or dominant particular gene allele as a cause. But, while schitzophrenia and bipolar disorder seem related to the total number of these random variations in the genome, autism seems more related to where these variations are located, rather than their overall frequency.